The Chemokine SDF-1/CXCL12 Binds to and Signals through the Orphan Receptor RDC1 in T Lymphocytes*

By K. Balabanian, B. Lagane, S. Infantino, K. Chow, Julie Harriague, B. Moepps, F. Arenzana‐Seisdedos, M. Thelen, F. Bachelerie. Journal of Biological Chemistry, 2005

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Combined phylogenetic and chromosomal location studies suggest that the orphan receptor RDC1 is related to CXC chemokine receptors. RDC1 provides a co-receptor function for a restricted number of human immunodeficiency virus (HIV) isolates, in particular for the CXCR4-using HIV-2 ROD strain. Here we show that CXCL12, the only known natural ligand for CXCR4, binds to and signals through RDC1. We demonstrate that RDC1 is expressed in T lymphocytes and that CXCL12-promoted chemotaxis is inhibited by an anti-RDC1 monoclonal antibody. Concomitant blockade of RDC1 and CXCR4 produced additive inhibitory effects in CXCL12-induced T cell migration. Furthermore, we provide evidence that interaction of CXCL12 with RDC1 is specific, saturable, and of high affinity (apparent KD ≈ 0.4 nm). In CXCR4-negative cells expressing RDC1, CXCL12 promotes internalization of the receptor and chemotactic signals through RDC1. Collectively, our data indicate that RDC1, which we propose to rename as CXCR7, is a receptor for CXCL12.

Subfields: Immunology, Oncology, Virology

View Paper: https://www.semanticscholar.org/paper/6bee856804c8a9dcbea73c870deb38cc37a71788

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Citations in the corpus

Abrogation of TGF beta signaling in mammary carcinomas recruits Gr-1+CD11b+ myeloid cells that promote metastasis. (2008, background): “In addition to CXCR4, CXCR7 has been identified as another signaling receptor for SDF-1 (Balabanian et al., 2005; Burns et al., 2006).”
Control of chemokine-guided cell migration by ligand sequestration. (2008, background): “The demonstration that CXCR7 is a receptor for SDF-1 (Balabanian et al., 2005; Burns et al., 2006) ended the seemingly monogamous relationships between this chemokine and its first-to-be-identified receptor CXCR4.”
Role of chemokines in tumor growth. (2007, background): “While SDF-1 interaction with CXCR4 results in chemotaxis [53,54], in the case of CXCR7 it mediates proliferation [55].”
The SDF-1-CXCR4 signaling pathway: a molecular hub modulating neo-angiogenesis. (2007, background): “Recently, a new SDF-1 receptor named CXCR7 has been discovered [66,67].”
CXCL12/CXCR4/CXCR7 Chemokine Axis and Cancer Progression (2010, background): “The CXCR7/RDC-1 gene maps to mouse chromosome 1 and human chromosome 2, where the genes encoding CXCR1, CXCR2, and CXCR4 are located.”
International Union of Basic and Clinical Pharmacology. LXXXIX. Update on the Extended Family of Chemokine Receptors and Introducing a New Nomenclature for Atypical Chemokine Receptors (2014, neutral): “Of importance for its biologic function, ACKR3 has ~10-fold higher affinity than CXCR4 for CXCL12 (Crump et al., 1997; Balabanian et al., 2005a; Burns et al., 2006).”
The role of CXC chemokines and their receptors in cancer. (2008, background): “[129] K.”
The chemokine and chemokine receptor superfamilies and their molecular evolution (2006, background): “[26] reported the identification of a second human receptor (RDC-1) that binds CXCL12, the characterization of this receptor is on going, but it may also bind CXCL11.”